AI-based characterization of multiple sclerosis clinical symptomatology using lesion parenchymal fraction: empirical support for the topographical model of MS (P3-3.018)

Objective:

To evaluate the relationship between lesion location, functional systems, and disability using an artificial intelligence (AI) model.

Background:

The topographical model of MS depicts localized lesion burden in a pool of variable neurological reserve, with the cervical cord at the shallow end.

Design/Methods:

63 people with MS (30 RRMS, 33 SPMS, 51 female, baseline age 45.8±10.0 yrs) were longitudinally evaluated with MRI and clinical metrics (EDSS and functional system scores [FSS]) with median 2 time points, max. 8, (total: 154), follow-up 2.1±2.5 years. Imaging: icobrain was used to measure T2-FLAIR lesions on brain MRI, and adapted to measure T2 lesion volumes in cervical cord. To create a lesion/reserve ratio, localized lesion volume percentiles were divided by regional parenchymal volume percentile (cerebral, infratentorial, cervical cord), yielding regionally-specific lesion parenchymal fraction (LPF). Modeling: in 500 iterations, Random Forest (RF) regression models were trained to estimate cross-sectional EDSS and FSS. Estimations were Spearman correlated with actual scores; median correlation was assessed. To evaluate role of LPF, two estimator sets were used: 1) simple model: age and sex, 2) full model: age, sex, and topographical LPF.

Results:

Spearman correlations between fitted and true clinical scores were highest for overall EDSS (R=0.29), pyramidal (R=0.37), bowel/bladder (R=0.38), and cerebellar (R=0.27). Models including LPF outperformed the simple model in 100%, 100%, 98%, and 91% of iterations, respectively. The EDSS and pyramidal FSS were most strongly associated with infratentorial LPF, which also most strongly predicted conversion to SPMS.

Conclusions:

Lesion localization can be mapped to specific functional systems to explicate MS heterogeneity. Lesion parenchymal fraction, an assessment of lesion load/parenchymal volume ratio, is a quantified expression of the topographical model of MS and may be a useful MRI correlate of MS clinical symptoms. Using this metric, AI techniques can be refined to identify specific thresholds for conversion to SPMS. Disclosure: Dr. Krieger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Krieger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Krieger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Krieger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Krieger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Krieger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Krieger has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Expert Witness. The institution of Dr. Krieger has received research support from Novartis. The institution of Dr. Krieger has received research support from Bristol Myers Squibb. Thibo Billiet has received personal compensation for serving as an employee of icometrix. Miss Maes has received personal compensation for serving as an employee of icometrix. Dr. De Barros has received personal compensation for serving as an employee of Icometrix. Dr. Van Hecke has received personal compensation for serving as an employee of icometrix. Annemie Ribbens, 9599 has received personal compensation for serving as an employee of icometrix. Annemie Ribbens, 9599 has stock in icometrix. Chenyu Wang, 7886 has received personal compensation for serving as an employee of Sydney Neuroimaging Analysis Centre. The institution of Chenyu Wang, 7886 has received research support from Multiple Sclerosis Research Australia. Kain Kyle has received personal compensation for serving as an employee of Sydney Neuroimaging Analysis Centre. Kain Kyle has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sydney Neuroimaging Analysis Centre. Linda Ly has nothing to disclose. Dr. Garber has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Garber has received research support from Trish MS Foundation. Michael Barnett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sydney Neuroimaging Analysis Centre. An immediate family member of Michael Barnett has received stock or an ownership interest from RxMx. The institution of Michael Barnett has received research support from Genzyme Sanofi. The institution of Michael Barnett has received research support from Biogen. The institution of Michael Barnett has received research support from Novartis.